Susceptibility to experimentally induced inflammatory diseases, including various forms of experimental autoimmune arthritis, varies substantially among inbred rat strains. For example, Lewis (Lew) and Dark agouti (DA) are generally highly susceptible to streptococcal cell wall, adjuvant and collagen arthritis, whereas Fischer (F344), Brown Norway (BN) and other strains are relatively resistant. We are interested in defining the mechanisms that functionally underlie these divergent patterns of susceptibility and resistance to various forms of experimentally induced inflammatory diseases, particularly arthritis, because this information may provide insights into human autoimmune inflammatory diseases. We have previously reported data indicating that the divergent disease expression may, in part, be a consequence of deficiency in hypothalamic-pituitary-adrenal axis (HPA) responsiveness in susceptible strains (e.g., Lewis) compared to resistant strains (e.g., F344). We continue to generate data confirming the importance of the HPA axis in disease susceptibility. In the carrageenin air-pouch model, we showed that corticosteroid antagonists increase severity of inflammation in F344 rats to a level equivalent to that of Lewis rats, whereas the antagonists have minimal effects in Lewis rats, reflecting their defects in corticosteroid production (Karalis K et al., Endocrinology 136:3107, 1995). In the same model, we also obtained data supporting our view that somatostatin may participate in the antiinflammatory actions of corticosteroids (Karalis K et al., Endocrinology 136:4133, 1995). Our observations regarding the neuroendocrine differences among autoimmune-susceptible and -resistant rat strains have also led us to explore TH1 AND TH2 cytokine expression in these rats. It is known that corticosteroids inhibit expression of TH1 cytokines such as gamma-interferon but have much lesser effects on the expression of TH2 cytokines such as IL-4 and IL-10. In collaboration with Dr. Rachel Caspi, NEI, we have observed that autoimmune disease-prone Lewis rats readily produce large numbers TH1 cytokine-expressing effector cells in response to uveitic autoantigen challenge in vivo, whereas F344 rats generate a more balanced TH1/TH2 cytokine profile (Caspi RR et al. J. Immunol., 1996, in press). We have suggested that these differences in cytokine expression may be linked to the neuroendocrine differences in these rat strains. In the course of this work, we also developed a simplified, competitive RT-PCR method for measuring rat cytokines (Sun, B. et al. J. Immunol. Methods., 1996, in press).